Dennis G. Fry

Validation of diacyl glycerolacyltransferase I as a novel target for the treatment of obesity and dyslipidemia using a potent and selective small molecule inhibitor.

A highly potent and selective DGAT-1 inhibitor was identified and used in rodent models of obesity and postprandial chylomicron excursion to validate DGAT-1 inhibition as a novel approach for the treatment of metabolic diseases. Specifically, compound 4a conferred weight loss and a reduction in liver triglycerides when dosed chronically in DIO mice and depleted serum triglycerides following a lipid challenge in a dose-dependent manner, thus, reproducing major phenotypical characteristics of DGAT-1(-/-) mice.

A Novel Stimulus, Oncogene, Induces Expression of CD80 (B7-1) Gene

CD80, a cell surface molecule found on antigen-presenting cells which particpates in costimulatory signaling, is frequently detected on transformed and tumor cells. We examined the effect of transformation by v-myc, k-ras, and SV40 T antigen oncogenes on the expression of a CD80 promoter/luciferase gene as well as the endogenous CD80 promoter gene in murine fibroblast cell lines. All three transformed cell lines were tumorigenic in nude mice, however expression of the CD80/luciferase transgene or endogenous CD80 was detected only in the v-myc and k-ras transformed cell lines. In both cell lines, CD80 expression was first detected more than 30 passages after transformation. Therefore, induction of CD80 expression was a late event following transformation and was not essential for the establishment of the transformed phenotype.

Repertoire cloning process, products derived therefrom and uses for said products

A repertoire cloning process for producing mammalian monoclonal antibodies. Also provided are methods for using these monoclonal antibodies, and kits which contain these monoclonal antibodies.